MARBLE
Activity and safety of atezolizumab plus carboplatin and paclitaxel in patients with advanced or recurrent thymic carcinoma (MARBLE): a multicentre, single-arm, phase 2 trial
Phase 2N = 48
- Population
- Adults (20 years or older) with histologically confirmed Masaoka stage III, IVA or IVB thymic carcinoma not amenable to definitive treatment, or recurrent thymic carcinoma after definitive treatment, with no previous systemic drug therapy for thymic carcinoma. All patients were Asian.
- Design
- Single-arm, multicentre phase 2 trial at 15 hospitals in Japan, funded by Chugai Pharmaceutical. Atezolizumab 1200 mg, carboplatin AUC 6 and paclitaxel 200 mg/m2 intravenously every 3 weeks for up to six cycles, then atezolizumab 1200 mg every 3 weeks for up to 2 years until progression or unacceptable toxicity. Enrolment 14 June 2022 to 6 July 2023. Primary endpoint: objective response rate by independent central review, assessed (with safety) in the per-protocol set. Registered at the Japan Registry of Clinical Trials (jRCT2031220144); the abstract prints no ClinicalTrials.gov number.
- Primary endpoint
- ORR
- Arms
- Atezolizumab with carboplatin and paclitaxel (experimental, n = 48): Atezolizumab 1200 mg, carboplatin AUC 6 and paclitaxel 200 mg/m2 every 3 weeks for up to six cycles, then atezolizumab 1200 mg every 3 weeks for up to 2 years
- People
- Shukuya T
Show the numbers
| Endpoint | Analysis | Atezolizumab with carboplatin and paclitaxel | Control | Effect |
|---|---|---|---|---|
| ORRPer-protocol set (all 48 enrolled patients) | primarymedian follow-up 15.3 monthsShukuya 2025 | 56% (41–71%) | — | P<0.000127 of 48 patients (56%) had a partial response; p value from Fisher's exact test. Median follow-up 15.3 months (IQR 13.8-16.6). The PMDA review report prints the same primary analysis (central review, RECIST 1.1, data cutoff 6 July 2024) as 56.3% (95% CI 41.2-70.5, Clopper-Pearson), against a prespecified threshold response rate of 30%, with 27 partial responses, 20 stable disease and 1 progressive disease; it also reports median overall survival at that analysis as not estimable (95% CI 19.2 to not estimable). Grade 3 or worse adverse reactions: neutropenia 27 (56%), leukopenia 16 (33%), febrile neutropenia 11 (23%), maculopapular rash 6 (13%). No treatment-related deaths; 8 deaths overall. |
| Endpoint | Analysis | Atezolizumab with carboplatin and paclitaxel | Control | Effect |
|---|---|---|---|---|
| ORRPer-protocol set (all 48 enrolled patients) | primarymedian follow-up 15.3 monthsShukuya 2025 | 56% (41–71%) | — | P<0.000127 of 48 patients (56%) had a partial response; p value from Fisher's exact test. Median follow-up 15.3 months (IQR 13.8-16.6). The PMDA review report prints the same primary analysis (central review, RECIST 1.1, data cutoff 6 July 2024) as 56.3% (95% CI 41.2-70.5, Clopper-Pearson), against a prespecified threshold response rate of 30%, with 27 partial responses, 20 stable disease and 1 progressive disease; it also reports median overall survival at that analysis as not estimable (95% CI 19.2 to not estimable). Grade 3 or worse adverse reactions: neutropenia 27 (56%), leukopenia 16 (33%), febrile neutropenia 11 (23%), maculopapular rash 6 (13%). No treatment-related deaths; 8 deaths overall. |